Hindawi Publishing Corporation

Case Reports in Pediatrics

Volume 2016, Article ID 4598587, 3 pages
http://dx.doi.org/10.1155/2016/4598587

Case Report
Autoimmune Hemolytic Anemia and Hodgkin’s Disease:
An Unusual Pediatric Association

Maria Miguel Gomes,1 Tereza Oliva,2 and Armando Pinto2

1
Department of Pediatrics, Hospital de Braga, Sete Fontes, São Victor, 4710-243 Braga, Portugal
2
Department of Pediatrics, Portuguese Oncology Institute of Porto Francisco Gentil, 4200-072 Porto, Portugal

Correspondence should be addressed to Maria Miguel Gomes; mariamgomes@hotmail.com

Received 30 November 2015; Revised 24 December 2015; Accepted 30 December 2015

Academic Editor: Maria Moschovi

Copyright © 2016 Maria Miguel Gomes et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.

Autoimmune hemolytic anemia (AIHA) is a recognized complication of lymphoproliferative disorders. AIHA associated with
Hodgkin’s disease (HD) is uncommon especially in the pediatric population. The diagnosis of AIHA is usually associated with
HD at the time of initial presentation or during the course of disease, but it could precede it by years to months. In adults the
association of AIHA and HD is more frequent in advanced stages and in the nodular sclerosis and mixed cellularity type HD.
Warm immune hemolytic anemia is mainly controlled with steroids and chemotherapy. We report a case of a pediatric patient with
direct antiglobulin positive test at the diagnosis of a late relapse of stage III B mixed cellularity type HD.

1. Introduction AIHA is usually associated with HD at the time of initial

presentation or during the course of disease, but it could
Autoimmune hemolytic anemia (AIHA) is an acquired clin- precede it by years to months [3, 4].
ical condition which is characterized by the production In adults the association of AIHA and HD is more
of autoantibodies that bind to the surface of circulating frequent in advanced stages (III and IV) and in the nodular
erythrocytes, leading to hemolysis and decreased survival sclerosis and mixed cellularity type HD [2, 3].
of the red blood cells [1, 2]. The direct antiglobulin test We report here a case of DAT positive AIHA at the
(DAT) is considered to be a cornerstone in establishing the diagnosis of a late relapse of stage III B mixed cellularity type
diagnosis of AIHA, since there is uptake of autoantibodies HD.
and/or complement components onto the affected red blood
cells [1, 2]. In less than 5 percent of the pediatric AIHA cases,
DAT is negative due to low amount of IgG on the erythrocytes 2. Case Description
[1, 2]. A 4-year-old female child presented with bilateral cervical
Hodgkin’s disease (HD) classically presents with lymph lymphadenopathy with six-month duration associated with
node enlargement with or without B symptoms (unexplained intermittent fever and night sweats. She was previously
weight loss exceeding 10% of body weight in 6 months, fever, healthy and there was no family history of oncologic or
and drenching night sweats) [2]. Anemia is a common man- immunologic diseases. On examination she had a left supr-
ifestation of HD and different mechanisms which contribute aclavicular lymph node of 3 cm (long axis) and a left cluster
to anemia include anemia of chronic disease, reduced red cell of lymph nodes of 6 cm (long axis). Both were nontender
survival, bone marrow infiltration, AIHA, and bone marrow and firm. Spleen was palpable, firm, and nontender below the
suppression by chemotherapy [2]. costal margin. The rest of the examination was unremark-
AIHA is a recognized complication of lymphoprolifera- able. Complete blood cell count was normal: hemoglobin
tive disorders [2, 3]. AIHA associated with HD is uncommon concentration 12.0 g/dL, hematocrit 39%, mean corpuscular
especially in the pediatric population [3]. The diagnosis of volume 81 fL, mean corpuscular hemoglobin 32.1 pg, white
2 Case Reports in Pediatrics

Table 1: Hematologic values.

Values at Values after 1 cycle

Parameters Values 1 month later Reference
presentation of treatment
Hemoglobin concentration 9.4 8.0 12.3 Lower limit of normal, 12.0 g/dL
Hematocrit 33.5 26 38.2 Lower limit of normal, 36%
Mean corpuscular volume 73.5 75 80.7 Lower limit of normal, 78 fL
Mean corpuscular hemoglobin 21.1 24 28 Lower limit of normal, 28 pg
Reticulocytes 10% 9% 1 0.5–2.5%
Iron 24 26 30 23–123 𝜇mol/L
Total iron-binding capacity 39.1 40.5 55 54–68 𝜇mol/L
Ferritin 254 463 150 12–150 𝜇g/L
Leukocytes 10.3 × 103 9.9 × 103 4.0 × 103 5.0–14.5 × 103 /𝜇L
Neutrophils 6.9 × 103 5.4 × 103 1.5 × 103 1.0–8.5 × 103 /𝜇L
Lymphocytes 1.8 × 103 2.3 × 103 2.0 × 103 1.5–8.0 × 103 /𝜇L
Platelets 341 × 103 239 × 103 200 × 103 200–450 × 103 /𝜇L

blood cell count 4.9 × 109 /L, and platelet count 309 × cell count 7.5 × 109 /L, and platelet count 279 × 109 /L.
109 /L. Sedimentation rate was elevated (66/106 mm on first She did not respond to the treatment with iron hydroxide
and second hour). Immunoglobulins were in the normal 6 mg/kg/day (Table 1). One month later she presented with
range and viral serologies were negative for Cytomegalovirus, fever and abdominal pain and still had microcytic and
herpes simplex I and herpes simplex II, varicella-zoster, hypochromic anemia (Table 1). On examination she had a
Hepatitis A, B, and C Virus, Human Immunodeficiency nontender mass on the umbilical region of 4 cm (long axis)
Virus, and Epstein Barr Virus. Computed tomography (CT) and hepatosplenomegaly. The rest of the examination was
scans revealed multiple cervical, supraclavicular, mediastinal, unremarkable. The CT scans revealed a cluster of lumbar-
lumbar-aortic, mesenteric, and hepatic hilar lymph node aortic lymph nodes of 5.6 × 4 cm between the superior
enlargement, of maximum 3 cm (long axis) and homoge- mesenteric artery and the bifurcation of the iliac arteries
neous splenomegaly (10 cm long axis). Scintigraphy with and mild hepatosplenomegaly. The PET scan showed intense
gallium-67 citrate showed diffused fixation on cervical and fixation of the abdominal mass and lumbar-aortic lymph
left supraclavicular lymph nodes. Bone marrow aspiration nodes. Bone marrow aspiration was normocellular. Bone
and bone marrow biopsy were normal. Biopsy of cervical marrow biopsy revealed erythroid hyperplasia. Laboratory
lymph node showed immunophenotype positive for CD30 investigations showed normal lactate dehydrogenase, liver
and CD15, and negative for CD45, CD20, CD2, CD3, function, total and indirect bilirubin, alanine and aspartate
epithelial membrane antigen (EMA), and anaplastic lym- transaminase, and immunoglobulins. Viral serology was neg-
phoma kinase (ALK). Histological examination confirmed ative. Peripheral blood smear showed markedly anisocytosis,
the diagnosis of stage III B of mixed cellularity type HD. polychromasia, and spherocytosis. The DAT was positive for
According to the German Society of Pediatric Oncology and IgG and C3d and a diagnosis of AIHA was made. Biopsy of
Hematology Hodgkin Lymphoma Trial 95 (GPOH-HD 95), the abdominal mass confirmed late relapse of the previous
the patient received two intensive cycles of chemotherapy diagnosed mixed cellularity type HD.
with vincristine 1.5 mg/m2 /day, procarbazine 100 mg/m2 /day, According to the relapse treatment in EuroNet Pediatric
prednisone 60 mg/m2 /day, and Adriamycin 40 mg/m2 /day Hodgkin’s Disease Group, the patient completed two cycles
(OPPA) and two cycles of cyclophosphamide 600 mg/m2 /day, of chemotherapy with ifosfamide 2000 mg/m2 /day, etoposide
vincristine 1.4 mg/m2 /day, procarbazine 100 mg/m2 /day, and 125 mg/m2 /day, and prednisolone 100 mg/m2 /day (IEP) and
prednisone 60 mg/m2 /day (COPP). A partial remission (PR) also two cycles with Adriamycin 25 mg/m2 /day, bleomycin
was obtained and the treatment proceeded with 16 Gy mantle 10 mg/m2 /day, vinblastine 6 mg/m2 /day, and dacarbazine
radiotherapy (from the upper cervical region till the medi- 375 mg/m2 /day (ABVD). The treatment proceeded with
astinum). In the posttreatment evaluation, the CT scans were 28.8 Gy lumbar-aortic and splenic hilum radiotherapy. A
normal and the 18-Fluorodeoxyglucose Positron Emission complete remission was obtained in the posttreatment eval-
Tomography (PET) scan was negative. uation. The CT scans showed a hypodense nodular lesion of
She was evaluated in periodic follow-up consultations 2 cm near the left renal hilum and the PET scan was negative.
and remained asymptomatic with no hematological or imag- After the first cycle, the hemoglobin level returned to normal
ing alterations. values (Table 1). Prednisolone reduction was attempted after
Seven years later, the 11-year-old child presented with 4 weeks and slow tapering was continued for three months.
microcytic and hypochromic anemia: hemoglobin concen- The patient was evaluated in periodic follow-up con-
tration 9.4 g/dL, hematocrit 33.5%, mean corpuscular volume sultations. In the last follow-up, being 14 years old, she
73.5 fL, mean corpuscular hemoglobin 21.1 pg, white blood remained with sustained complete remission: asymptomatic
Case Reports in Pediatrics 3

with no other autoimmune conditions and no hematological Authors’ Contribution

or imaging alterations.
Maria Miguel Gomes, Tereza Oliva, and Armando Pinto
collected the patient’s clinical data, analyzed the data, and
wrote the paper.
3. Discussion
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Conflict of Interests Principles and Practice, vol. 14, no. 3, pp. 205–207, 2005.

The authors declare that there is no conflict of interests

regarding the publication of this paper.